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European sea bass (Dicentrarchus labrax) is a widely consumed marine fish in Mediterranean areas, and different farming techniques are applied for fish culturing to satisfy the growing demand for seafood. The aim of this study was to investigate the effects of conventional and organic feed on the quality of cultured European sea bass (Dicentrarchus labrax) collected during the growth period. The concentrations of ash, moisture, essential macro-elements (Ca, K, Mg, Na and P), micro-elements (Co, Cr, Cu, Fe, Mn, Ni and Zn) and toxic elements (As, Cd, and Pb) were determined in feeds and in fillets of cultured fish. The results were compared to those obtained from wild sea bass. Results showed that the differences between organic diet-fed and conventional diet-fed sea basses varied in relation to the specific element measured and the growth period. The former showed higher concentration of Fe, Mg and Cr, and lower Na content. The amount of P, Na, Fe, Cu and Cr in wild sea bass was significantly (P ≤ 0.05) higher than that found in farmed fish. The levels of toxic elements in cultured sea bass were always within the allowed limit for fishery products. Wild samples had significantly (P ≤ 0.05) higher content of arsenic and lead than farmed sea bass. Cultured fish represent a valuable dietary source of essential macro- and micro-elements. Controlled rearing systems and feedings were related to a decrease in the presence of some toxic metals in cultured fish compared with wild fish.

In all vertebrates, mature oocytes arrest at the metaphase of the II meiotic division, while some invertebrates arrest at metaphase-I, others at prophase-I. Fertilization induces completion of meiosis and entry into the first mitotic division. Several experimental models have been considered from both vertebrates and invertebrates in order to shed light on the peculiar aspects of meiotic division, such as the regulation of the cytostatic factor (CSF) and the maturation promoting factor (MPF) in metaphase I or II. Recently, we proposed the oocytes of ascidian Ciona intestinalis as a new model to study the meiotic division. Here, taking advantage of the recent publication of the C. intestinalis genome, we presented a phylogenetic analysis of key molecular components of the CSF-related machinery. We showed that the Mos/MAP kinase pathway is perfectly conserved in ascidians. We demonstrated the presence of a CSF-like activity in metaphase-I arrested C. intestinalis oocytes able to block cell division in two-cell embryos. We further investigated the regulation of CSF by demonstrating that both CSF and MPF inactivation, at the exit of metaphase-I, are independent from protein synthesis, indicating the absence of short-lived factors that regulate metaphase stability, as in other invertebrate species. The results obtained suggest that meiotic regulation in C. intestinalis resembles that of vertebrates, such as Xenopus accordingly to the position of this organism in the evolutionary tree.

Moderate beer consumption can be considered as part of a healthy diet since it may protect against heart disease, cancer and osteoporosis. The protective effects of beer reside in its polyphenol content whose chemical composition appears extremely complex. In the present study, five commercial beers with different polyphenol content (ranging between 690 - 2400 μM equivalents of quercetin) were employed to investigate their cytotoxic effect in vitro on HL-60 cells derived from a human promyelocytic leukemia cell line. A significant reduction in cell viability was measured after 48 hours treatment. Lyophilized beers with higher polyphenol content showed the highest cytotoxicity compared to those with lower concentrations. However, when the assay was performed applying equal amounts of total polyphenols from different lyophilized beers, the sample possessing lowest amount of polyphenols (690 μM equivalents of quercetin) resulted the most effective in reducing cell viability. These data suggest that the biological activities of polyphenols present in beer are not simply dependent upon their total concentration, but qualitative profile and relative concentrations are even more important in determining their antiproliferative effects on cancer cells.

SummarySeveral genetic and physiological factors increase the risk of DNA damage in mammalian oocytes. Two critical events are: (i) meiosis progression, from maturation to fertilization, due to extensive chromatin remodelling during genome decondensation; and (ii) aging, which is associated with a progressive oxidative stress. In this work, we studied the transcriptional patterns of three genes,RAD51,APEX-1andMLH1, involved in DNA repair mechanisms. The analyses were performed by real-time quantitative PCR (RT-qPCR) in immature andin vitromatured oocytes collected from 17 ± 3-month-old heifers and 94 ± 20-month-old cows. Batches of 30–50 oocytes for each group (three replicates) were collected from ovarian follicles of slaughtered animals. The oocytes were freed from cumulus cells at the time of follicle removal, or afterin vitromaturation (IVM) carried out in M199 supplemented with 10% fetal calf serum, 10 IU luteinising hormone (LH)/ml, 0.1 IU follicle-stimulating hormone (FSH)/ml and 1 μg 17β-oestradiol/ml. Total RNA was extracted by Trizol method. The expression of bovineGAPDHgene was used as the internal standard, while primers for bovineRAD51,APEX-1andMLH1genes were designed from DNA sequences retrieved from GenBank. Results obtained indicate a clear up-regulation ofRAD51,APEX-1andMLH1genes after IVM, ranging between two- and four-fold compared with germinal vesicle (GV) oocytes. However, onlyRAD51showed a significant transcript increase between the immature oocytes collected from young or old individuals. This finding highlightsRAD51as a candidate gene marker for discriminating bovine immature oocytes in relation to the donor age.

Increased consumption of fruit and vegetables can represent an easy strategy to significantly reduce the incidence of cancer. We recently demonstrated that the flavonoid quercetin, naturally present in the diet and belonging to the class of phytochemicals, is able to sensitize several leukemia cell lines and B cells isolated from patients affected by chronic lymphocytic leukemia (B-CLL), in addition to apoptotic inducers (anti-CD95 and rTRAIL). Further, it potentiates the effect of fludarabine, a first-line chemotherapeutic drug used against CLL. The proapoptotic activity of quercetin in cell lines and B-CLL is related to the expression and activity of Mcl-1-antiapoptotic proteins belonging to the Bcl-2 family. Quercetin downregulates Mcl-1 mRNA and protein levels acting on mRNA stability and protein degradation. Considering the low toxicity of the flavonoids toward normal peripheral blood cells, our experimental results are in favor of a potential use of quercetin in adjuvant chemotherapy in CLL or other types of cancer.

In the present study, we report that polyphenols present in red wine obtained by a controlled microvinification process are able to protect human erythrocytes from oxidative stress and to activate Plasma Membrane Redox System (PMRS). Human plasma obtained from healthy subjects was incubated in the presence of whole red wine at a concentration corresponding to 9.13-73 μg/ml gallic acid equivalents to verify the capacity to protect against hypochlorous acid (HOCl)-induced plasma oxidation and to minimize chloramine formation. Red wine reduced hemolysis and chloramine formation induced by HOCl of 40 and 35%, respectively. PMRS present on human erythrocytes transfers electrons from intracellular molecules to extracellular electron acceptors. We demonstrated that whole red wine activated PMRS activity in human erythrocytes isolated from donors in a dose-dependent manner with a maximum at about 70-100 μg/ml gallic acid equivalents. We also showed that red wine increased glutathione (GSH) levels and erythrocytic antioxidant capacity, measured by 2,2-diphenyl-1-picrylhydrazyl (DPPH) quenching assay. Furthermore, we reported that GSH played a crucial role in regulating PMRS activity in erythrocytes. In fact, the effect of iodoacetamide, an alkylating agent that induces depletion of intracellular GSH, was completely counteracted by red wine. Bioactive compounds present in red wine, such as gallic acid, resveratrol, catechin, and quercetin were unable to activate PMRS when tested at the concentrations normally present in aged red wines. On the contrary, the increase of PMRS activity was associated with the anthocyanin fraction, suggesting the capacity of this class of compounds to positively modulate PMRS enzymatic activity.

Novel therapies for rheumatoid arthritis also include the use of naturally occurring compounds possessing antioxidant properties. In the present work, the effects of oral administration of quercetin were investigated in a rat model of adjuvant arthritis. Arthritis was induced by a single intradermal injection of heat-inactivated Mycobacterium butyricum in incomplete Freund's adjuvant. The experimental groups were treated with an oral daily dose of 150 mg/kg b.w. of quercetin for 28 days. Results indicated that quercetin was able to ameliorate all markers of inflammation and oxidative stress measured. Quercetin lowered levels of interleukin-1β, C-reactive protein, and monocyte chemotactic protein-1 and restored plasma antioxidant capacity. In addition, quercetin inhibited the enzymatic activity of pro-inflammatory 12/15-lipoxygenase in lung and liver and increased the expression of heme oxygenase-1 in joint and lung of arthritic rats. Finally, quercetin inhibited the 2-fold increase of NF-қB activity observed in lung, liver and joint after induction of arthritis.

Over the past decades, extensive studies have addressed the therapeutic effects of omega-3 polyunsaturated fatty acids (omega-3 FAs) against different human diseases such as cardiovascular and neurodegenerative diseases, cancer, etc. A growing body of scientific research shows the pharmacokinetic information and safety of these natural occurring substances. Moreover, during recent years, a plethora of studies has demonstrated that omega-3 FAs possess therapeutic role against certain types of cancer. It is also known that omega-3 FAs can improve efficacy and tolerability of chemotherapy. Previous reports showed that suppression of nuclear factor-kappa B, activation of AMPK/SIRT1, modulation of cyclooxygenase (COX) activity, and up-regulation of novel anti-inflammatory lipid mediators such as protectins, maresins, and resolvins, are the main mechanisms of antineoplastic effect of omega-3 FAs. In this review, we have collected the available clinical data on the therapeutic role of omega-3 FAs against breast cancer, colorectal cancer, leukemia, gastric cancer, pancreatic cancer, esophageal cancer, prostate cancer, lung cancer, head and neck cancer, as well as cancer cachexia. We also discussed the chemistry, dietary source, and bioavailability of omega-3 FAs, and the potential molecular mechanisms of anticancer and adverse effects.

Quercetin (3,3',4',5,7-pentahydroxyflavone) is one of the major dietary flavonoid, found in a broad range of fruits, vegetables and beverages, such as tea and wine, with a daily uptake between 10 and 100 mg depending on the dietary attitude. We previously demonstrated that quercetin sensitizes HPB-ALL cell line to CD95-mediated apoptosis through a mechanism independent of its antioxidant properties and related to its ability to regulate the activity of serine-threonine protein kinases. Here, we report that quercetin is an inhibitor of protein kinase CK2, a kinase involved in apoptotic resistance in several forms of leukemia. Quercetin inhibits CK2 in an in vitro assay and in HPB-ALL cells decreasing its activity of 3.5-fold within 12 h from treatment, in good agreement with the intracellular concentration of the molecule measured by HPLC on the same cells (0.933 +/- 0.188 mu g/mg of total proteins). Quercetin also inhibits pure CK2 enzyme with an EC50 of about 150 nM in an in vitro assay. A specific CK2 inhibitor, TBB (4,5,6,7-tetra-bromo-benzo-triazole), behaves similarly to quercetin since it abolishes CK2 activity in HPB-ALL cells, but fails to enhance CD95-mediated apoptosis when associated with an anti-CD95 monoclonal antibody mimicking CD95 ligand. The resistance to apoptotic induction in HPB-ALL can be bypassed taking advantage of the pleiotropic activity of quercetin. Combined treatments which include quercetin in association with death receptor inducers may represent a novel therapeutic strategy against leukemia. (C) 2014 Elsevier Ltd. All rights reserved.

Increased consumption of fruits and vegetables can represent an easy strategy to significantly reduce the incidence of cancer. From this observation, derived mostly from epidemiological data, the new field of chemoprevention has emerged in the primary and secondary prevention of cancer. Chemoprevention is defined as the use of natural or synthetic compounds able to stop, reverse, or delay the process of tumorigenesis in its early stages. A large number of phytochemicals are potentially capable of simultaneously inhibiting and modulating several key factors regulating cell proliferation in cancer cells. Quercetin is a flavonoid possessing potential chemopreventive properties. It is a functionally pleiotropic molecule, possessing multiple intracellular targets, affecting different cell signaling processes usually altered in cancer cells, with limited toxicity on normal cells. Simultaneously targeting multiple pathways may help to kill malignant cells and slow down the onset of drug resistance. Among the different substrates triggered by quercetin, we have reviewed the ability of the molecule to inhibit protein kinases involved in deregulated cell growth in cancer cells.

Increased consumption of fruits and vegetables can represent an easy strategy to significantly reduce the incidence of cancer. From this observation, derived mostly from epidemiological data, the new field of chemoprevention has emerged in the primary and secondary prevention of cancer. Chemoprevention is defined as the use of natural or synthetic compounds able to stop, reverse, or delay the process of tumorigenesis in its early stages. A large number of phytochemicals are potentially capable of simultaneously inhibiting and modulating several key factors regulating cell proliferation in cancer cells. Quercetin is a flavonoid possessing potential chemopreventive properties. It is a functionally pleiotropic molecule, possessing multiple intracellular targets, affecting different cell signaling processes usually altered in cancer cells, with limited toxicity on normal cells. Simultaneously targeting multiple pathways may help to kill malignant cells and slow down the onset of drug resistance. Among the different substrates triggered by quercetin, we have reviewed the ability of the molecule to inhibit protein kinases involved in deregulated cell growth in cancer cells.

Until recently, the supposed preventive effects of red wine against cardiovascular diseases, the so-called "French Paradox", has been associated to its antioxidant properties. The interest in the anticancer capacity of polyphenols present in red wine strongly increased consequently to the enormous number of studies on resveratrol. In this study, using lyophilized red wine, we present evidence that its anticancer effect in a cellular model is mediated by apoptotic and autophagic cell death. Using a human osteosarcoma cell line, U2Os, we found that the lyophilized red wine was cytotoxic in a dose-dependent manner with a maximum effect in the range of 100-200 mu g/ml equivalents of gallic acid. A mixed phenotype of types I/II cell death was evidenced by means of specific assays following treatment of U2Os with lyophilized red wine, e.g., autophagy and apoptosis. We found that cell death induced by lyophilized red wine proceeded through a mechanism independent from its anti-oxidant activity and involving the inhibition of PI3K/Akt kinase signaling. Considering the relative low concentration of each single bioactive compound in lyophilized red wine, our study suggests the activation of synergistic mechanism able to inhibit growth in malignant cells.

Regular consumption of fruit and vegetables is associated with reduced risks of cancer, cardiovascular disease and other aging-related diseases. Convincing evidence exists suggesting that an increased fruit, vegetables, and grains consumption is a relatively easy and practical strategy to significantly reduce the incidence of chronic diseases. Cancer chemoprevention intends to interrupt the carcinogenesis process, which includes initiation, promotion and progression of otherwise normal cells to reduce cancer. The development of diet-derived constituents represents one of the major goals in cancer chemoprevention. A key question is whether a purified phytochemical has the same protective effects as does the whole food or mixture of foods in which the phytochemical is present. Putative chemopreventive agents are identified on the basis of epidemiological and in vitro and in vivo studies. All these compounds present tumor-suppressing properties in animal models of carcinogenesis, and they interfere with cellular processes involved in tumor formation. Phase I clinical trials have been completed only for few of these phytochemicals, and pilot phase II-III trials are planned. In the revised version of this review originally published in 2005 on this journal (Russo et al., Dietary Phytochemicals in Chemoprevention of Cancer. Immunology, Endocrine & Metabolic Agents in Medicinal Chemistry, 2005, 5, 61-72), we updated data regarding the description of the mechanisms by which these compounds exert their biological activities. Finally, we also reviewed in details data regarding well-known and promising chemopreventive phytochemicals.

Increased consumption of fruit and vegetables can represent an easy strategy to significantly reduce the incidence of cancer. We recently demonstrated that the flavonoid quercetin, naturally present in the diet and belonging to the class of phytochemicals, is able to sensitize several leukemia cell lines and B cells isolated from patients affected by chronic lymphocytic leukemia (B-CLL), in addition to apoptotic inducers (anti-CD95 and rTRAIL). Further, it potentiates the effect of fludarabine, a first-line chemotherapeutic drug used against CLL. The proapoptotic activity of quercetin in cell lines and B-CLL is related to the expression and activity of Mcl-1-antiapoptotic proteins belonging to the Bcl-2 family. Quercetin downregulates Mcl-1 mRNA and protein levels acting on mRNA stability and protein degradation. Considering the low toxicity of the flavonoids toward normal peripheral blood cells, our experimental results are in favor of a potential use of quercetin in adjuvant chemotherapy in CLL or other types of cancer.

Biochemical and genetic studies on cellular and animal models on the mechanism(s) of action of phytochemicals provide a functional explanation of how and why a diet rich in fruits and vegetables is considered healthy. It is not unusual to find molecules that protect against diseases, which greatly differ from a physiopathological point of view, such as cancer and cardiovascular disorders. Quercetin falls into this category and possesses a broad range of biological properties. Uptake, metabolism and circulating concentrations of quercetin and its metabolites suggest that a regular diet provides amounts of quercetin (10¼M) by supplementation with quercetin-enriched foods or supplements. Multiple lines of experimental evidence suggest a positive association between quercetin intake and improved outcomes of inflammatory cardiovascular risk. The ameliorating effect of quercetin administration can be extended to other chronic inflammatory disorders but only if supplementation occurs in patients. Quercetin can be considered the prototype of a naturally-occurring chemopreventive agent because of its key roles in triggering the "hallmarks of cancer". However, several critical points must be taken into account when considering the potential therapeutic use of this molecule: (1) pharmacological versus nutraceutical doses applied, (2) specificity of its mechanism of action compared to other phytochemicals, and (3) identification of "direct" cellular targets. The design of specific clinical trials is extremely warranted to depict possible applications of quercetin in adjuvant cancer therapy. Copyright © 2011 Elsevier Inc. All rights reserved.

International audience; The eukaryotic Initiation Factor 2 (eIF2) is a key regulator of protein synthesis in eukaryotic cells, implicated in the initiation step of translation. Fertilization of the sea urchin eggs triggers a rapid increase in protein synthesis activity, which is necessary for the progress into embryonic cell cycles. Here we demonstrate that fertilization triggers eIF2α dephosphorylation, concomitant with an increase in protein synthesis and that induction of the eIF2α phosphorylation is intimately linked with an inhibition of protein synthesis and cell cycle arrest. Using a phospho-mimetic protein microinjected into sea urchin eggs, we showed that dephosphorylation of eIF2α is necessary for protein synthesis activity and cell division progression following fertilization. Our results demonstrate that regulation of eIF2α plays an important role in the protein synthesis rise that occurs during early development following fertilization.

Events of reproduction occurring from meiotic resumption of the immature oocyte up to its exit from the second meiotic block following activation will be revealed. Morphological modifications of the oocyte during maturation will be related to signal transduction mechanisms involving primary or secondary messengers. A detailed view will be addressed to genetic and epigenetic control of oocyte maturation. At fertilization, reciprocal gamete activation and novel knowledge related to sperm factor and cascade mechanisms occurring in the oocyte will be focused. A detailed description of ion currents occurring during fertilization will depict another point of view of oocyte activation mechanisms, further supporting for their complexity. Finally, all basic information related to this short time lapse will be considered in relation to clinical application of assisted reproductive technologies. New frontiers, such as stem cells and cloning technologies, will be analyzed and future applications and improvements will be hypothesised.

In most of vertebrates, mature oocytes arrest at the metaphase of the II meiotic division, while some invertebrates arrest at metaphase-I, others at prophase-I. Fertilization induces completion of meiosis and entry into the first mitotic division. Several experimental models have been considered from both vertebrates and invertebrates in order to shed light on the peculiar aspects of meiotic division, such as the regulation of the cytostatic factor (CSF) and the maturation promoting factor (MPF) in metaphase I or II. Here, we reviewed the role of CSF and MPF and their biochemical pathways in regulating meiosis completion. Differences and similarities existing within several model systems of invertebrates, such as ascidians, cnidarians, mollusks, starfish, will be analyzed and compared to meiotic regulation in Xenopus. Data will be analyzed at the light of the phylogenetic conservation of MPF and CSF functions, accordingly to the position of these organisms in the evolutionary tree.

In recent years, the impact of sperm DNA damage on fertility has become an important issue. The different technologies developed to check sperm DNA fragmentation lead to the same conclusion: DNA damage negatively impacts upon reproductive processes. Oocyte DNA repair capacity is one of the cues to understanding embryo developmental arrest. APEX/Ref-1 (apurinic/apyrimidic endonuclease) is an enzyme involved in the DNA base excision repair pathway removing the abasic sites, the most common DNA decays. In humans, APEX has a multifunctional role, including the control of the redox status of transcription factors. RT-PCR allowed us to detect human APEX transcripts in oocytes, spermatozoa and preimplantation blocked embryos. In parallel, a comparative study on sea squirt Ciona intestinalis (ascidian) indicated that APEX transcripts are clearly detectable in oocytes and embryos until the larva stage, but not in spermatozoa, suggesting the appearance of the paternal contribution to DNA repair during development having arisen only late in Vertebrate evolution. Of additional phylogenetic significance is the observation that sea squirt APEX appears to lack redox transcriptional activity.